The present invention is directed to a method of racemizing optically-active amino alcohols to convert the less desired enantiomer to the racemic mixture in high yields.
Various amino alcohols which have a pair of optically active enantiomers are known in which one of the pair has little or no utility while the other has utility in its own right or is useful as a precursor for the synthesis of pharmaceutical agents and the like. For example, of the optically active pair of 2-amino-1-butanol, the levorotatory compound has no utility while the dextrorotatory compound is a starting material for the medicament, Ethambutol.
It is highly desired to have a simple process to convert the less valuable material into the more valuable material. Previous attempts have required anhydrous conditions, the use of hard to handle reagents, the formation of by-products which reduced the yield and hindered separation and recovery of the desired enantiomer and/or provide for low degree of racemization. For example, in an article entitled "A Study on the Racemization of Optically Active-Amino Alcohols" by Seong-Ho Kang, published in Hanguk Saenghiral Kwahak Yonguwan Nouchoung, Vol. 25, p. 9-14 (1980) one is taught that the optical rotation of 2-amino-1-butanol can be changed by treating it with a hydrogenation catalyst in the presence of hydrogen and ammonia. The reference teaches that crystalline by-products form when nickel or cobalt catalysts are used while the by-products are reduced when a specific cobalt-iron oxide which is high in iron content is employed. Japanese Patent Application Sho 51/6911 describes the same conversion but indicates that the best results are obtained by using a reductive cobalt or Urishibara cobalt as the catalyst. These catalysts are formed for example, by depositing a cobalt salt on a substrate and reducing the salt to cobalt metal by treatment with a reducing agent such as zinc, hydrogen or carbon monoxide to produce a supported cobalt catalyst. Both references' methods require the use of ammonia which is both difficult to handle and to dispose of and, therefore, adds to the processing costs.
It is highly desired to provide a process which causes a high degree of racemization, low by-product formation and avoids the need for difficult to handle reagents such as ammonia.